Is nephrocalcin related to the urinary derivative (bikunin) of inter‐α‐trypsin inhibitor?

Tang, Yunhua; Grover, Phulwinder K.; Moritz, Robert L.; Simpson, Richard J.; Ryall, Rosemary L.

doi:10.1111/j.1464-410x.1995.tb07738.x

Cited by 40 publications

(37 citation statements)

References 31 publications

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“…Because ORG has a similar expression pattern and identical struc ture features to NC, Desbois et al [29] proposed that ORG is the gene coding for NC in the kidney. More recently [99], NC was recognized as a fragment (HI-14) of the light chain of Ial, the bikunin, on the basis of SDS-PAGE. inhibitory, and gel filtration properties and amino acid sequence of its two peptides.…”

Section: Nephrocalcinmentioning

confidence: 99%

Interactions between Stone-Forming Calcific Crystals and Macromolecules

Khan¹

1997

Urol Int

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Section: Nephrocalcinmentioning

confidence: 99%

Interactions between Stone-Forming Calcific Crystals and Macromolecules

Khan¹

1997

Urol Int

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“…Comparison of partial amino acid sequence of UAP, bikunin, and other related proteins. I, N-terminal sequence of bikunin according to [34]; 11, the first 25 amino acids of UAP before treatment with chondroitinase AC; 111, the first 25 amino acids of UAP after treatment with chondroitinase AC; IV, amino acid sequence of the 35-kDa protein isolated by Ryall's group [27]; V, amino acid sequence of the 21-kDa protein isolated by Ryall's group [27] which is claimed to be nephrocalcin. molecular masses.…”

Section: Discussionmentioning

confidence: 99%

“…Because ORG has a similar expression pattern and identical structural features to nephrocalcin, the authors proposed that ORG is the gene coding for nephrocalcin in kidney. More recently, Ryall's group purified nephrocalcin by using the same procedures described by the original authors [27], and isolated two proteins with calcium oxalate crystallization inhibitory activity. One of them had J molecular mass of 35 kDa as estimated by using SDS/PAGE.…”

Section: : a V L P Q E E E G X G G G Q L V T E V T K K E D S C Q L mentioning

confidence: 99%

“…Concerning UAP, the inhibitory activity of this glycoprotein was not affected by chondroitinase AC treatment, but was completely destroyed after treatment with pronase using the same Sgrensen's procedure [lo, 121. In ,a recent study [27], Ryall's group isolated two urinary inhibitors of calcium oxalate crystallization with a molecular masses of 35 and 21 kDa. The partial amino acid sequence of the 35-kDa inhibitor matched that of bikunin.…”

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confidence: 99%

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Identification of Uronic‐Acid‐Rich Protein as Urinary Bikunin, the Light Chain of Inter‐α‐Inhibitor

Atmani

Mizon

Khan

1996

European Journal of Biochemistry

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Uronic-acid-rich protein (UAP) is a urinary glycoprotein that inhibits calcium oxalate crystallization in vitro. It shows a structural similarity to bikunin, a component of inter-a-inhibitor (Id) known for its inhibition of the action of many serine proteinases like trypsin and chymotrypsin. To clarify the relationship between these macromolecules, UAP, IaI, urinary bikunin, and plasma bikunin were purified and studied. Their calcium oxalate crystallization inhibitory activity was assayed before and after treatment with chondroitinase AC and pronase. Their molecular mass was determined by using SDS/PAGE before and after these treatments. Polyclonal bikunin antibody was used on Western blots for immunological identification. The partial amino acid sequence of UAP before and after chondroitinase treatment was determined. Also, the antitryptic activity of UAP was measured and compared to that of bikunin, which is responsible for the antiprotease activity of IaI. UAP exhibited a strong calcium oxalate crystallization inhibitory activity. I d and both bikunins were less inhibitory. Chondroitinase AC had no effect on inhibitory activity of these proteins even when their molecular mass changed. However, after pronase treatment, the inhibitory activity of both bikunins and UAP was completely destroyed. The antitryptic activity of UAP was found to be 0.78 U/mg which is lower than that of bikunin which is about 1.9 U/mg. On Western blotting, bikunin antibody immunoreacted with UAP and both urinary and plasma bikunins. Partial amino acid sequence confirmed the identity of UAP as urinary bikumin.Keywords: nephrolithiasis ; calcium oxalate ; inter-a-inhibitor ; uronic-acid-rich protein ; bikunin.Kidneys excrete a urine normally supersaturated with respect to many salts including calcium oxalate, the most common compound found in kidney stones [l, 21. But normal urine does not support crystallization because of the presence of many natural inhibitors. Purification, identification, and characterization of such macromolecules have been the object of extensive studies [3 -91. Among these inhibitors is uronic-acid-rich protein (UAP), a glycoprotein of 35 kDa isolated from human [3] and rat urine [ 101 which strongly inhibits calcium oxalate crystallization in vitro. The same inhibitor isolated from the urine of stone formers showed less inhibitory activity when compared to that purified from the urine of healthy subjects [ll]. This result suggests a structural abnormality of UAP obtained from stone-forming patients. Interestingly, both human and rat UAP exhibited structural similarity to bikunin, a subunit of inter-a-inhibitor ( I d ) [lo, 121. Indeed, the sequence of the first 18 amino acid residues of UAP was identical to I d and bikunin. Furthermore, on Western blotting, the immuoreaction between UAP and I d antibody was positive [lo].IaI, with a molecular mass of approximately 220 kDa, is one of the plasma protease inhibitors known formerly as inter-a-trypsin inhibitor (ITI be the active part of I d involved in the inhibition...

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“…This notion combined with advances in protein chemistry has led to many investigations into the physicochemical processes of stone formation. [1,2]. Among the known urinary macromolecular substances including Tamm-Horsfall glycoprotein [3], uronic acid rich protein (UAP) [4] and urinary prothrombin fragment 1 [5], nephrocalcin may be the principal inhibitor in urine [6] since it accounts for approximately 90% of the total inhibitory effect of urine on CaOx crystallization [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Heparan Sulfate(HS)/Heparan Sulfate Proteoglycan(HSPG) and Bikunin are Up-regulated During Calcium Oxalate Nephrolithiasis in Rat Kidney.

et al. 2002

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Summary: We reported that expression of both HSPG and of bikunin are increased in calcium oxalate (CaOx) nephrolithic rat kidneys (lida et al., J. Am. Soc. Nephrol. 1999, Urol. Res.1997). However, these findings were obtained from separate experiments. The present study evaluates whether levels of HSPG and bikunin expression differ in the rat kidney during calcium oxalate nephrolithiasis. Twenty-four male Wistar rats weighing 200-250 g were assigned to one of four groups (n=6 each group) and administered with 0.5% ethylene glycol daily and 0.5 pg of 1 a-OH-D3 every other day to induce CaOx nephrolithiasis. Animals were sacrificed 1 or 2 weeks later and both kidneys were excised. The cortex was separated from the medulla and papillary tips in the right kidney, then stored in liquid nitrogen for quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR). The left kidney was fixed in 10% buffered formalin for histochemical studies. We assessed the variable gene expression of both HSPG and bikunin by QC-RT-PCR. Immunohistochemical analyses of left kidney tissue samples determined the localization of HSPG and bikunin. Normal rats serving as controls (n=6 each) were also sacrificed and processed in the same manner as the experimental groups. QC-RT-PCR confirmed that HSPG and bikunin mRNA expression is significantly increased in nephrolithic kidneys (p<0.05; MannWhitney test), and that medulla and papillary tips tended to express more mRNA of both. Immunohistochemical studies revealed that the production of HS and bikunin was increased in both the distal and proximal tubules of nephrolithic kidneys. These findings suggest that the increased expression of both HSPG and bikunin play an important role during calcium oxalate stone formation. In addition, this phenomenon might be associated with the progression of urothelial damage.

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Is nephrocalcin related to the urinary derivative (bikunin) of inter‐α‐trypsin inhibitor?

Abstract: NC represents a portion of the light chain of ITI, although this conclusion must remain tentative until confirmed using authentic NC.

Cited by 40 publications

References 31 publications

Interactions between Stone-Forming Calcific Crystals and Macromolecules

Interactions between Stone-Forming Calcific Crystals and Macromolecules

Identification of Uronic‐Acid‐Rich Protein as Urinary Bikunin, the Light Chain of Inter‐α‐Inhibitor

Heparan Sulfate(HS)/Heparan Sulfate Proteoglycan(HSPG) and Bikunin are Up-regulated During Calcium Oxalate Nephrolithiasis in Rat Kidney.

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